Method for treating roundworm infestations in animals

ABSTRACT

A formulation for treating and preventing roundworm infestations in horses, dogs, cats, and other animals is provided. This formulation includes an agent effective against nematodes, wherein the agent is pyrantel, morantel, any salt thereof, or any combination thereof. Preferably, the formulation additionally includes an agent effective against nematodes and obligate parasitic flies, an edible non-aqueous liquid and a thickening agent. The formulation of the present invention allows for a high concentration of the agent effective against nematodes and for the treatment of roundworms, particularly ascarids, that have become resistant to at least one agent typically effective against nematodes.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. patent applicationSer. No. 10/623,954, filed Jul. 21, 2003, which is a divisional of U.S.patent application Ser. No. 09/723,846, filed on Nov. 28, 2000, which isnow U.S. Pat. No. 6,596,714, which is a continuation of U.S. patentapplication Ser. No. 09/573,513, filed on May 18, 2000, which is nowissued as U.S. Pat. No. 6,207,179. Each application and patent listedabove is incorporated by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] Not Applicable.

BACKGROUND OF THE INVENTION

[0003] The present invention relates to a formulation for treating,controlling and preventing parasitic worm infestations and a method formaking the formulation. More specifically, the present invention relatesto a combination roundworm and tapeworm parasiticide for use in horsesand household pets.

[0004] Several types of parasites, including cestodes, nematodes andobligate parasitic insects, particularly flies, commonly plague horses,dogs and cats. Cestodes are flatworms and include, for example,tapeworms, while nematodes are roundworms. Avermectins and milbemycinsare nematocidal agents commonly used in the treatment and control ofparasitic roundworm infestations in equines, including domestic horses,donkeys, mules and zebras, as well as in companion animals, namely catsand dogs. These agents are also effective against obligate parasiticflies. Contrary to popular belief among animal owners, however, theseagents are ineffective against tapeworm infestations. Rather, tapeworminfestations must be controlled and treated by a cestocidal agent.

[0005] Studies have shown that misinformation about tapeworm treatmentand control is common among horse owners. Many horse owners evidentlybelieve that ivermectin, an avermectin used for treating and controllingroundworm infestations, is effective in controlling tapeworminfestations as well. This misinformation may account for a rise in theprevalence of certain tapeworms. A particular equine tapeworm whoseprevalence is on the rise is Anoplocephala perfoliata.

[0006] Tapeworms are pervasive parasites that appear to infect at leasthalf of all mature horses. Post-mortem studies have shown that, ingeneral, at least 50% of mature horses in many populations are infectedwith A. perfoliata. A. perfoliata is a type of tapeworm that can infectall types of equine animals. Adult A. perfoliata attach to the posteriorregions of the equine intestinal tract. The highest concentration is inthe cecal wall but a fair amount attach to the terminal ilium andventral colon as well. The greatest concentration of A. perfoliata, andthus the greatest associated damage, occurs at the ileocecal junction.A. perfoliata infestation increases the incidence of spasmodic colon andileal impaction in horses. Tapeworms also have been implicated as acause of cecal and ileocecal intussusceptions in young horses. Thelatter conditions are potentially fatal and can be remedied only bycomplicated and expensive abdominal surgery.

[0007] There are only a few classes of drugs which are effective in thetreatment, control and prevention of tapeworm infestations. Among theseclasses are praziquantel, pyrantel and morantel compounds. Parasiticidalformulations have been disclosed which contain praziquantel combinedwith a variety of roundworm controlling agents. One such formulation isdisclosed in U.S. Pat. No. 5,824,653 to Beuvry et al. The compoundswhich result from these combinations, however, may be dangerous aspraziquantel has been shown to be toxic at levels other than lowdosages. Additionally, praziquantel purportedly is bitter to tastemaking it unpalatable and thus undesirable in ingestable formulations,for example, pastes.

[0008] Pyrantel and morantel compounds are currently believed by thoseskilled in the art to offer an inadequate substitute to praziquantel inthe treatment and control of tapeworm infestations. Pyrantel saltsgenerally either are only partially effective against tapeworms at theirlabel dosages (e.g., pyrantel pamoate) or must be administered in dailyregimes (e.g., pyrantel tartrate). Further, pyrantel pamoate offers alow suspended solids content when in paste form, the highest percentageencountered being about 43.95% weight per weight (w/w). A paste with alow suspended solids content contains less active ingredient per unitthan a paste with a higher suspended solids content. Therefore, a highervolume of paste must be delivered to the animal in order to achieve thesame therapeutic effect.

[0009] Accordingly, there remains a need in the veterinary industry fora combination parasiticidal formulation containing both a cestocidalagent and an agent effective against nematodes and obligate parasiticflies that is less toxic than formulations containing praziquantel.Further, a palatable combination parasiticide is needed foradministration in ingestable forms. The primary objective of thisinvention is to meet these needs.

BRIEF SUMMARY OF THE INVENTION

[0010] According to the present invention, the foregoing and otherobjects are achieved by a parasiticidal formulation that includes amixture of an edible non-aqueous liquid, a thickening agent, a firstagent effective against nematodes and obligate parasitic flies and asecond agent effective against nematodes and cestodes, wherein thesecond agent is pyrantel, morantel, any salt thereof, or any combinationthereof. Preferably the first agent effective against nematodes andobligate parasitic flies is an avermectin, a milbemycin, a derivativethereof, or any combination thereof. Another aspect of the presentinvention is a method of making this parasiticidal formulation. Thismethod includes mixing the above-mentioned components. A further aspectof the present invention is a method for administering the parasiticidalformulation of the present invention to an animal. This method ofadministration includes providing the parasiticidal formulationdescribed above in the form of a paste and administering it to an animalfor ingestion.

[0011] Objects of the invention, together with the advantages and novelfeatures appurtenant thereto, will be set forth in part in thedescription which follows, and in part will become apparent to thoseskilled in the art upon examination of the following, or may be learnedfrom the practice of the invention. The objects and advantages of theinvention may be realized and attained by means of the instrumentalitiesand combinations particularly pointed out in the appended claims.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

[0012] The parasiticidal formulation of the present invention is aneffective ingestable formulation for the treatment and control ofcestode, nematode and obligate parasitic fly infestations in equine andcompanion animals. Such animals include, but are not limited to, horses,donkeys, mules, zebras, dogs and cats. The formulation includes anedible, non-aqueous liquid, a thickening agent, a first agent fortreating and controlling roundworm and obligate parasitic flyinfestations and a second agent, which is a cestocidal agent, fortreating and controlling roundworm and tapeworm infestations. Thismixture provides a unique formulation in which the agent effectiveagainst nematodes and obligate parasitic flies is allowed to dissolvesubstantially into solution while the cestocidal agent remains generallysuspended. Thus, the system allows for delivery of two differentparasiticidal agents in two different physical states simultaneously ina single oral formulation.

[0013] The second agent of the present invention includes pyrantel,morantel, any salt of pyrantel or morantel, or any combination thereof.These compounds offer advantages over praziquantel in the control andtreatment of tapeworm infestations in that they have a higher dosagesafety margin than praziquantel. Pyrantel pamoate, a salt of pyrantel,for example, should present little to no adverse reaction when ingestedby horses in a concentration equivalent to two to five times the labelrecommended dosage. Further, pyrantels are desirable because horseowners are familiar with this group of compounds. Additionally, pyranteland morantel are more palatable than praziquantel as these compounds donot share the bitter taste associated with praziquantel.

[0014] Preferably, the second agent of the present invention is a saltof pyrantel. Pyrantel salts that may be used in the formulation of thepresent invention include, but are not limited to, pyrantel pamoate,pyrantel tartrate or any combination thereof. Preferably, the secondagent of the present invention is pyrantel pamoate. Pyrantel pamoate, atsufficiently high dosages, eliminates and controls infestations by avariety of tapeworms, including Anoplocephala perfoliata.

[0015] Pyrantel pamoate usually is classified as a nematocidal agentrather than a cestocidal agent at its recommended label dosage of about6.6 milligrams per kilogram of animal. At this dosage, pyrantel pamoatehas only partial activity in the treatment and control of tapeworminfestations. Effectiveness percentages from about 65% to 100% againstcestode infestations have been shown with paste formulations, theaverage being about 85% efficacy. However, at about twice the labelrecommended dosage or higher, pyrantel pamoate exhibits tapewormcontrolling activity unattainable by many cestocidal compounds at anydosage. It has been observed that at an elevated dosage of about twotimes the label recommended dosage, or about 13.2 milligrams perkilogram of animal, pyrantel pamoate exhibits between about 93% and97.8% efficacy in horses infected with A. perfoliata. At an elevateddosage of about three times the label recommended dosage, or about 19.8milligrams per kilogram of animal, pyrantel pamoate is about 100%effective in treating cestode infestations. Consequently, theparasiticidal formulation of the present invention includesconcentrations of pyrantel pamoate at about two to three times thedosage recommended for treatment and control of roundworm infestations.

[0016] When the cestocidal agent chosen is pyrantel pamoate, theformulation of the present invention preferably may include about 40-75%w/w pyrantel pamoate (a total of about 14-26% w/w pyrantel in theformulation). More preferably, the formulation of the present inventionmay include about 50-65% w/w pyrantel pamoate (a total of about 17-23%w/w pyrantel in the formulation). Formulations containing othercestocidal agents besides pyrantel pamoate are also contemplated by thisinvention, as discussed above. If a different pyrantel compound is used,preferably the formulation would contain pyrantel in an amount similarto the amounts discussed above.

[0017] As noted above, at elevated dosages, pyrantel pamoate serves bothas a nemotocidal agent and a cestocidal agent. Additional agents whichare effective against nematodes and obligate parasitic flies that may beused in the formulation of the present invention include, but are notlimited to, avermectins, milbemycins, any derivative thereof, or anycombination thereof. Avermectins that may be used in the formulation ofthe present invention include, but are not limited to, abamectin,doramectin, eprinomectin, ivermectin, moxidectin, selamectin, or anycombination thereof. These agents are most effective when substantiallydissolved in solution, i.e., when at least about 90% of the agentpresent is dissolved. Thus, it is preferred that these agents becombined with a solvent before being administered to an animal.Preferably the first agent used in the formulation of the presentinvention is ivermectin. Ivermectin kills a variety of roundwormsincluding stomach worms, intestinal worms, lungworms, barber's poleworms, lice and mites, as well as bots and grubs of obligate parasiticflies.

[0018] When the first agent chosen is ivermectin, the formulation of thepresent invention preferably may include about 0.10-10% w/w ivermectin.More preferably, the formulation of the present invention may includeabout 0.25-0.35% w/w ivermectin.

[0019] When using ivermectin and pyrantel pamoate in combination, theparasiticidal formulation of the present invention preferably mayinclude about 0.2-1.0% w/w ivermectin and about 45-65% w/w pyrantelpamoate. More preferably, the formulation of the present invention mayinclude about 0.2-0.5% w/w ivermectin and about 50-60% w/w pyrantelpamoate.

[0020] The edible, non-aqueous liquid that may be used in theformulation of the present invention includes, but is not limited to,edible glycol polymers, edible oils, or any combination thereof. Edibleglycol polymers that may be used in the formulation of the presentinvention include, but are not limited to, propylene glycol,polyethylene glycol, glycerine (glycerol), glycerol formal, or anycombination thereof. Edible oils that may be used in the formulation ofthe present invention include, but are not limited to, Arachis oil(peanut oil), polyoxyl castor oils, soybean oil, or any combinationthereof. Preferably, the edible, non-aqueous liquid is propylene glycol.

[0021] The edible, non-aqueous liquid preferably is present in theparasiticidal formulation of the present invention in an amounteffective, in combination with the thickening agent, for substantiallydissolving a therapeutic amount of one or more agents effective againstnematodes and obligate parasitic flies while allowing one or morecestocidal agents to remain generally suspended. The agents effectiveagainst nematodes and obligate parasitic flies are substantiallydissolved in solution when at least about 90% of the agent present isdissolved. Cestocidal agents are generally suspended when less thanabout 10% of the agent present is dissolved. The formulation of thepresent invention preferably may include a total of about 40-50% w/wedible, non-aqueous liquid. More preferably, the formulation of thepresent invention may include about 42-46% w/w edible, non-aqueousliquid.

[0022] The thickening agent that may be used in the formulation of thepresent invention includes, but is not limited to, carbomers,cornstarch, polyethylene, polyvinylpyrrolidones, edible clay, xanthangum, or any combination thereof. Preferably, the thickening agents are acarbomer and xanthan gum. A suitable carbomer is Carbomer 974Pmanufactured by B.F. Goodrich. The thickening agent preferably includesan amount that is effective, in combination with the edible, non-aqueousliquid, to substantially dissolve a therapeutic amount of one or moreagents effective against nematodes and obligate parasitic flies(preferably at least about 90% dissolved) while allowing one or morecestocidal agents to remain generally suspended (preferably less thanabout 10% dissolved). The formulation of the present inventionpreferably may include about 0.01-1.0% w/w thickening agent. Morepreferably, the formulation of the present invention may include about0.09-0.65% w/w thickening agent.

[0023] The combination of an edible, non-aqueous liquid and a thickeningagent to form the unique system of the present invention allows one ormore cestocidal agents to dissolve substantially while allowing one ormore agents effective against nematodes and obligate parasitic flies toremain generally suspended. As a result, the system of the presentinvention allows for delivery of two different parasiticidal agents intwo different physical states simultaneously in a single oralformulation. The combination of the edible, non-aqueous liquid and thethickening agent also functions to transport one or more cestocidalagents and one or more agents effective against nematodes and obligateparasitic flies into an animal in the physical state in which each ismost effective so that the agents may interact therapeutically withparasites in the animal. In animals with no parasite infestations uponadministration, the combination of the edible, non-aqueous liquid andthe thickening agent functions to transport one or more cestocidalagents and one or more agents effective against nematodes and obligateparasitic flies into an animal in the physical state in which each ismost effective so that the animal is protected from subsequentinfestations by certain parasites.

[0024] Further, the formulation of the present invention allows forhigher suspended solids content for some cestocidal agents than wasforeseen as being possible from the prior art. For example, theformulation of the present invention allows for a paste containingpyrantel pamoate having a suspended solids content of up to about 70%w/w, with a preferred concentration of about 54.13% w/w. The highestconcentration previously encountered in a paste containing pyrantel wasabout 43.95% w/w. The higher suspended solids content allows for asignificantly smaller volume of paste to be administered, making iteasier to deliver higher dosages of pyrantel than when previouslyavailable formulations are used.

[0025] As discussed above, cestocidal agents and agents effectiveagainst nematodes and obligate parasitic flies each provide protectionagainst different species of parasites. Thus, when a cestocidal agentand an agent effective against nematodes and obligate parasitic fliesare combined in a single parasiticidal formulation, the formulationprovides protection against a broader spectrum of parasites than aformulation containing either parasiticidal agent alone. Theparasiticidal formulation of the present invention may be administeredeither to treat infected animals or to prevent infestations innon-infected animals. Preferably, the formulation is administered onceper month.

[0026] A number of optional ingredients may be added to enhance certainproperties of the formulation. One such optional ingredient is apreservative which acts to preserve both parasiticidal agents in thephysical state in which they are most effective. Preservatives that maybe used in the formulation of the present invention include, but are notlimited to, methylparaben, propylparaben, or any combination thereof.Preferably, the formulation of the present invention includes acombination of methylparaben and propylparaben in a ratio ofapproximately 10:1 respectively. If a combination of methylparaben andpropylparaben is chosen as a preservative for the formulation, theparasiticidal formulation of the present invention preferably mayinclude about 0.15-0.25% w/w methylparaben and about 0.015-0.025% w/wpropylparaben. More preferably, the parasiticidal formulation of thepresent invention may include about 0.18% w/w methylparaben and about0.02% w/w propylparaben.

[0027] Another optional ingredient that may be included in theformulation of the present invention is an additional solvent for theagent effective against nematodes and obligate parasitic flies.Preferably this solvent is water. Water may be present in aconcentration ranging from about 0-10% w/w depending upon theconcentration of edible, non-aqueous liquid used. The total amount ofsolvent should be sufficient to dissolve substantially all of the agenteffective against nematodes and obligate parasitic flies present in theformulation of the present invention while allowing all of thecestocidal agent to remain generally suspended.

[0028] One preferred formulation of the present invention includespyrantel pamoate, ivermectin, xanthan gum, carbomer, methylparaben,propylparaben and propylene glycol. Another preferred formulation of thepresent invention includes pyrantel pamoate, ivermectin, xanthan gum,carbomer and propylene glycol. A highly preferred formulation of thepresent invention which includes a preservative is described inExample 1. A highly preferred formulation of the present invention whichdoes not include a preservative is described in Example 2.

[0029] One parasiticidal formulation of the present invention is made bycombining an edible non-aqueous liquid, a thickening agent, a firstagent effective against nematodes and obligate parasitic flies and asecond agent effective against nematodes and cestodes to form a mixture.Preferably, ivermectin and pyrantel pamoate may be used respectively.The order in which components are added in making the formulation is notcritical. The formulation may optionally be heated to between about 60°and 80° C., continuously or intermittently, during its preparation inorder to dissolve the agent effective against nematodes and obligateparasitic flies more quickly. This process can be scaled to make anydesired quantity of the formulation.

[0030] One preferred method of making a parasiticidal formulation of thepresent invention includes placing a quantity of edible, non-aqueousliquid in a vessel and warming it to about 70° C. Next, a quantity of afirst agent effective against nematodes and obligate parasitic flies isadded, and the resulting solution is cooled to room temperature. Thesecond agent effective against nematodes and cestodes is then added andmixed with the solution for an effective period of time. The secondagent will not dissolve into solution but instead will remain generallysuspended throughout, i.e., less than about 10% will dissolve. Athickening agent is then added and mixed into the solution until itdissolves substantially, i.e., until at least 90% of the thickeningagent present is dissolved. Optionally, a preservative then may be addedand mixed into the solution until substantially dissolved, i.e., untilat least 90% of the preservative present is dissolved.

[0031] Preferably, the parasiticidal formulation of the presentinvention is administered as a paste formulation to any equine orcompanion animal. It is particularly useful for domestic horses,donkeys, mules, zebras, cats and dogs. Preferably, the paste is ingestedby the animal and is administered in a dosage of about 65-75 milligramsper kilogram of animal once per month.

[0032] The following are examples of various parasiticidal formulationsand methods of making these formulations that are within the scope ofthis invention. These examples are not meant in any way to limit thescope of this invention.

EXAMPLE 1

[0033] Propylene glycol, in a quantity amounting to 44.17% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, a quantity of ivermectin amounting to0.29% w/w of the final formulation was added to the propylene glycol andmixed with it until all of the ivermectin substantially dissolved. Theresulting solution was then cooled to room temperature. A quantity ofpyrantel pamoate amounting to 55.14% w/w of the final formulation(19.13% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. Next, a quantity ofxanthan gum amounting to 0.18% w/w of the final formulation was added tothe mixture. With continued agitation, Carbomer 974P was added to themixture in a quantity amounting to 0.02% w/w of the final formulation.Subsequently, methylparaben, in a quantity amounting to 0.18% w/w of thefinal formulation, was added to the mixture, followed by a quantity ofpropylparaben amounting to 0.02% w/w of the final formulation. Theresulting formulation is within the scope of the present invention andincludes two parasiticidal agents, each targeting different species ofparasites.

EXAMPLE 2

[0034] Propylene glycol, in a quantity amounting to 44.37% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, a quantity of ivermectin amounting to0.29% w/w of the final formulation was added to the propylene glycol andmixed with it until all of the ivermectin substantially dissolved. Theresulting solution was then cooled to room temperature. A quantity ofpyrantel pamoate amounting to 55.14% w/w of the final formulation(19.13% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. With continuedagitation, a quantity of xanthan gum amounting to 0.18% w/w of the finalformulation was added to the mixture. Subsequently, carbomer 974P wasadded to the mixture in a quantity amounting to 0.02% w/w of the finalformulation. The resulting formulation is within the scope of thepresent invention and includes two parasiticidal agents, each targetingdifferent species of parasites.

EXAMPLE 3

[0035] Propylene glycol, in a quantity amounting to 30% w/w of the finalformulation, was added to a vessel and warmed to 70° C. Agitation began.With continued agitation, water in a quantity amounting to 7.285% w/w ofthe final formulation, was added to the propylene glycol to form asolution. Next, a quantity of ivermectin amounting to 0.325% w/w of thefinal formulation was added to the solution and mixed with it until allof the ivermectin substantially dissolved. The resulting solution wasthen cooled to room temperature. A quantity of pyrantel pamoateamounting to 61.74% w/w of the final formulation (21.42% w/w of finalformulation as pyrantel) was then added and mixed with the solution. Thepyrantel pamoate did not dissolve in the solution but instead remainedgenerally suspended throughout. Lastly, a quantity of xanthan gumamounting to 0.65% w/w of the final formulation was added to themixture. The resulting formulation is within the scope of the presentinvention and includes two parasiticidal agents, each targetingdifferent species of parasites.

EXAMPLE 4

[0036] Propylene glycol, in a quantity amounting to 28% w/w of the finalformulation, was added to a vessel and warmed to 70° C. Agitation began.With continued agitation, water, in a quantity amounting to 9.285% w/wof the final formulation, was added to the propylene glycol to form asolution. Next, ivermectin amounting to 0.325% w/w of the finalformulation was added to the solution and mixed with it until all of theivermectin substantially dissolved. The resulting solution was thencooled to room temperature. A quantity of pyrantel pamoate amounting to61.74% w/w of the final formulation (21.42% w/w of final formulation aspyrantel) was then added and mixed with the solution. The pyrantelpamoate did not dissolve in the solution but instead remained generallysuspended throughout. Lastly, a quantity of xanthan gum amounting to0.65% w/w of the final formulation was added to the mixture. Theresulting formulation is within the scope of the present invention andincludes two parasiticidal agents, each targeting different species ofparasites.

EXAMPLE 5

[0037] Propylene glycol, in a quantity amounting to 32.0% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, water, in a quantity amounting to5.285% w/w of the final formulation, was added to the propylene glycolto form a solution. Next, ivermectin amounting to 0.325% w/w of thefinal formulation was added to the solution and mixed with it until allof the ivermectin substantially dissolved. The resulting solution wasthen cooled to room temperature. A quantity of pyrantel pamoateamounting to 61.74% w/w of the final formulation (21.42% w/w of finalformulation as pyrantel) was then added and mixed with the solution. Thepyrantel pamoate did not dissolve in the solution but instead remainedgenerally suspended throughout. Lastly, a quantity of xanthan gumamounting to 0.65% w/w of the final formulation was added to themixture. The resulting formulation is within the scope of the presentinvention and includes two parasiticidal agents, each targetingdifferent species of parasites.

EXAMPLE 6

[0038] Propylene glycol, in a quantity amounting to 37.836% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, water, in a quantity amounting to 7.0%w/w of the final formulation, was added to the propylene glycol to forma solution. Next, ivermectin amounting to 0.284% w/w of the finalformulation was added to the solution and mixed with it until all of theivermectin substantially dissolved. The resulting solution was thencooled to room temperature. A quantity of pyrantel pamoate amounting to54.03% w/w of the final formulation (18.75% w/w of final formulation aspyrantel) was then added and mixed with the solution. The pyrantelpamoate did not dissolve in the solution but instead remained generallysuspended throughout. With continued agitation, a quantity of xanthangum amounting to 0.65% w/w of the final formulation was added to themixture. Lastly, Carbomer 974P was added to the mixture in a quantityamounting to 0.02% w/w of the final formulation. The resultingformulation is within the scope of the present invention and includestwo parasiticidal agents, each targeting different species of parasites.

EXAMPLE 7

[0039] Propylene glycol, in a quantity amounting to 44.806% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, water, in a quantity amounting to 0.48%w/w of the final formulation, was added to the propylene glycol to forma solution. Next, ivermectin amounting to 0.284% w/w of the finalformulation was added to the solution and mixed with it until all of theivermectin substantially dissolved. The resulting solution was thencooled to room temperature. With continued agitation, a quantity ofpyrantel pamoate amounting to 54.03% w/w of the final formulation(18.75% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. Next, a quantity ofxanthan gum amounting to 0.2% w/w of the final formulation was added tothe mixture. Lastly, Carbomer 974P was added to the mixture in aquantity amounting to 0.2% w/w of the final formulation. The resultingformulation is within the scope of the present invention and includestwo parasiticidal agents, each targeting different species of parasites.

EXAMPLE 8

[0040] Propylene glycol, in a quantity amounting to 43.4% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, a quantity of ivermectin amounting to0.275% w/w of the final formulation was added to the propylene glycoland mixed with it until all of the ivermectin substantially dissolved.The resulting solution was then cooled to room temperature. A quantityof pyrantel pamoate amounting to 56.17% w/w of the final formulation(19.49% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. With continuedagitation, a quantity of xanthan gum amounting to 0.097% w/w of thefinal formulation was added to the mixture. Lastly, Carbomer 974P wasadded to the mixture in a quantity amounting to 0.097% w/w of the finalformulation. The resulting formulation is within the scope of thepresent invention and includes two parasiticidal agents, each targetingdifferent species of parasites.

EXAMPLE 9

[0041] Propylene glycol, in a quantity amounting to 44.14% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, a quantity of ivermectin amounting to0.29% w/w of the final formulation was added to the propylene glycol andmixed with it until all of the ivermectin substantially dissolved. Theresulting solution was then cooled to room temperature. A quantity ofpyrantel pamoate amounting to 55.17% w/w of the final formulation(19.14% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. Next, a quantity ofxanthan gum amounting to 0.1% w/w of the final formulation was added tothe mixture. With continued agitation, Carbomer 974P was added to themixture in a quantity amounting to 0.1% w/w of the final formulation.Subsequently, methylparaben, in a quantity amounting to 0.18% w/w of thefinal formulation, was added to the mixture, followed by a quantity ofpropylparaben amounting to 0.02% w/w of the final formulation. Theresulting formulation is within the scope of the present invention andincludes two parasiticidal agents, each targeting different species ofparasites.

EXAMPLE 10

[0042] Propylene glycol, in a quantity amounting to 49.705% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, a quantity of ivermectin amounting to0.235% w/w of the final formulation was added to the propylene glycoland mixed with it until all of the ivermectin substantially dissolved.The resulting solution was then cooled to room temperature. A quantityof pyrantel pamoate amounting to 49.7% w/w of the final formulation(17.25% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. Next, a quantity ofxanthan gum amounting to 0.135% w/w of the final formulation was addedto the mixture. With continued agitation, Carbomer 974P was added to themixture in a quantity amounting to 0.045% w/w of the final formulation.Subsequently, methylparaben, in a quantity amounting to 0.162% w/w ofthe final formulation, was added to the mixture, followed by a quantityof propylparaben amounting to 0.018% w/w of the final formulation. Theresulting formulation is within the scope of the present invention andincludes two parasiticidal agents, each targeting different species ofparasites.

EXAMPLE 11

[0043] Propylene glycol, in a quantity amounting to 38.199% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, a quantity of sterile water in aquantity amounting to 6.0% w/w of the final formulation was added to thepropylene glycol to form a solution. Next, ivermectin amounting to0.261% w/w of the final formulation was added to the solution and mixedwith it until all of the ivermectin substantially dissolved. Theresulting solution was then cooled to room temperature. A quantity ofpyrantel pamoate amounting to 55.14% w/w of the final formulation(19.13% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. With continuedagitation, a quantity of xanthan gum amounting to 0.1% w/w of the finalformulation was added to the mixture. With continued agitation, aquantity of Carbomer 974P was added to the mixture in a quantityamounting to 0.1% w/w of the final formulation. Lastly, methylparaben,in a quantity amounting to 0.18% w/w of the final formulation, was addedto the mixture, followed by a quantity of propylparaben amounting to0.02% w/w of the final formulation. The resulting formulation is withinthe scope of the present invention and includes two parasiticidalagents, each targeting different species of parasites.

EXAMPLE 12

[0044] Propylene glycol, in a quantity amounting to 44.19% w/w of thefinal formulation, was added to a vessel and warmed to 70° C. Agitationbegan. With continued agitation, a quantity of ivermectin amounting to0.261% w/w of the final formulation was added to the propylene glycoland mixed with it until all of the ivermectin substantially dissolved.The resulting solution was then cooled to room temperature. A quantityof pyrantel pamoate amounting to 55.14% w/w of the final formulation(19.13% w/w of final formulation as pyrantel) was then added and mixedwith the solution. The pyrantel pamoate did not dissolve in the solutionbut instead remained generally suspended throughout. Next, a quantity ofxanthan gum amounting to 0.15% w/w of the final formulation was added tothe mixture. With continued agitation, Carbomer 974P was added to themixture in a quantity amounting to 0.05% w/w of the final formulation.Lastly, methylparaben, in a quantity amounting to 0.18% w/w of the finalformulation, was added to the mixture, followed by a quantity ofpropylparaben amounting to 0.02% w/w of the final formulation. Theresulting formulation is within the scope of the present invention andincludes two parasiticidal agents, each targeting different species ofparasites.

[0045] From the foregoing it will be seen that this invention is onewell adapted to attain all ends and objectives herein-above set forth,together with the other advantages which are obvious and which areinherent to the invention.

[0046] Since many possible embodiments may be made of the inventionwithout departing from the scope thereof, is to be understood that allmatters herein set forth are to be interpreted as illustrative, and notin a limiting sense.

[0047] While specific embodiments have been shown and discussed, variousmodifications may of course be made, and the invention is not limited tothe specific forms or arrangement of parts and steps described herein,except insofar as such limitations are included in the following claims.Further, it will be understood that certain features andsub-combinations are of utility and may be employed without reference toother features and sub-combinations. This is contemplated by and iswithin the scope of the claims.

I claim:
 1. A method of treating and preventing infestations ofroundworms in animals, comprising: providing a parasiticidal formulationcomprising a mixture of (i) an edible non-aqueous liquid, (ii) athickening agent, (iii) a first agent effective against nematodes andobligate parasite flies, and (iv) a second agent effective againstnematodes, wherein said second agent is selected from the groupconsisting of pyrantel, morantel, any salt thereof and any combinationthereof; and orally administering said formulation as a paste to saidanimal in an amount therapeutically effective against said roundworms.2. The method of claim 1, wherein said roundworms are ascarids, andwherein said formulation is administered in an amount therapeuticallyeffective against said ascarids.
 3. The method of claim 2, wherein saidfirst agent is an avermectin.
 4. The method of claim 3, wherein saidascarids are resistant to avermectins, and wherein said formulation isadministered in an amount therapeutically effective against saidavermectin-resistant ascarids.
 5. The method of claim 4, wherein saidascarids are resistant to ivermectin, and wherein said formulation isadministered in an amount therapeutically effective against saidivermectin-resistant ascarids.
 6. The method of claim 5, wherein saidformulation is orally administered to a horse.
 7. The method of claim 5,wherein said second agent is pyrantel or a salt thereof.
 8. The methodof claim 7, wherein said first agent is ivermectin.
 9. The method ofclaim 1, wherein said roundworms are resistant to avermectins, andwherein said formulation is administered in an amount therapeuticallyeffective against said averemectin-resistant roundworms.
 10. The methodof claim 9, wherein said roundworms are resistant to ivermectin, andwherein said formulation is administered in an amount therapeuticallyeffective against said ivermectin-resistant roundworms.
 11. The methodof claim 9, wherein said second agent is effective against cestodes. 12.The method of claim 1, wherein said second agent is present in saidformulation in an amount equal to or greater than about 17% w/w.
 13. Themethod of claim 1, wherein said second agent is present as a salt, andsaid salt is present in said formulation in an amount equal to orgreater than about 50% w/w.
 14. A method of treating and preventinginfestations of roundworms in animals, comprising: providing aparasiticidal formulation comprising an agent effective againstnematodes, wherein said agent is selected from the group consisting ofpyrantel, morantel, and combinations thereof, and wherein said agent ispresent in said formulation in an amount equal to or greater than about17% w/w; and administering said formulation to said animal in an amounttherapeutically effective against said roundworms.
 15. The method ofclaim 14, wherein said roundworms are ascarids, and wherein saidformulation is administered in an amount therapeutically effectiveagainst said ascarids.
 16. The method of claim 15, wherein said ascaridsare resistant to avermectins, and wherein said formulation isadministered in an amount therapeutically effective against saidavermectin-resistant ascarids.
 17. The method of claim 16, wherein saidascarids are resistant to ivermectin, and wherein said formulation isadministered in an amount therapeutically effective against saidivermectin-resistant ascarids.
 18. The method of claim 17, wherein saidagent is present in said formulation in an amount equal to or greaterthan about 19% w/w.
 19. The method of claim 18, wherein said agent ispresent as a salt, and said salt is present in said formulation in anamount equal to or greater than about 50% w/w.
 20. The method of claim19, wherein said salt is selected from the group consisting of pyrantelpamoate, pyrantel tartrate and any combination thereof.
 21. The methodof claim 20, wherein said salt is pyrantel pamoate.
 22. The method ofclaim 17, wherein said formulation is administered to a horse.
 23. Themethod of claim 17, wherein said formulation is administered orally. 24.The method of claim 23, wherein said formulation is a paste.
 25. Themethod of claim 24, wherein said animal is a horse.
 26. A method oftreating and preventing infestations of roundworms in animals,comprising: providing a parasiticidal formulation comprising a mixtureof (i) an edible non-aqueous liquid that is an edible oil selected fromthe group consisting of Arachis oil, polyoxyl castor oil, soybean oiland any combination thereof, (ii) a thickening agent, (iii) a firstagent effective against nematodes and obligate parasite flies, and (iv)a second agent effective against nematodes, wherein said second agent isselected from the group consisting of pyrantel, morantel, any saltthereof and any combination thereof; and administering said formulationto said animal in an amount therapeutically effective against saidroundworms.
 27. A method of treating and preventing infestations ofroundworms in animals, comprising: providing a parasiticidal formulationcomprising a mixture of (i) an edible non-aqueous liquid that is anedible oil glycol polymer selected from the group consisting ofpropylene glycol, polyethylene glycol, glycerine, glycerol formal andany combination thereof, wherein said non-aqueous liquid is comprised ofabout 25-55% weight per weight proplylene glycol, (ii) a thickeningagent, (iii) a first agent effective against nematodes and obligateparasite flies, and (iv) a second agent effective against nematodes,wherein said second agent is selected from the group consisting ofpyrantel, morantel, any salt thereof and any combination thereof; andadministering said formulation to said animal in an amounttherapeutically effective against said roundworms.
 28. A method oftreating and preventing infestations of roundworms in animals,comprising: providing a parasiticidal formulation comprising a mixtureof (i) an edible non-aqueous liquid, (ii) a thickening agent selectedfrom the group consisting of a carbomer, cornstarch, polyethylene, apolyvinylpyrrolidone, and edible clay, xanthan gum and any combinationthereof, (iii) a first agent effective against nematodes and obligateparasite flies, and (iv) a second agent effective against nematodes,wherein said second agent is selected from the group consisting ofpyrantel, morantel, any salt thereof and any combination thereof; andadministering said formulation to said animal in an amounttherapeutically effective against said roundworms.
 29. A method oftreating and preventing infestations of roundworms in animals,comprising: providing a parasiticidal formulation comprising a mixtureof (i) an edible non-aqueous liquid, (ii) a thickening agent, (iii) afirst agent effective against nematodes and obligate parasite flies,(iv) a second agent effective against nematodes, wherein said secondagent is selected from the group consisting of pyrantel, morantel, anysalt thereof and any combination thereof, and (v) a preservativeselected from the group consisting of methylparaben, propylparaben andany combination thereof; and administering said formulation to saidanimal in an amount therapeutically effective against said roundworms.